Glucose utilization in Type 1 (insulin-dependent) diabetes: Evidence for a defect not reversible by acute elevations of insulin

Abstract

It has long been assumed that replacement of insulin in insulin-deficient diabetic patients will normalise glucose utilization. In this study, glucose utilization was measured in nine long-standing, poorly controlled diabetic patients and five control subjects, matched for age (33 +/- 3 versus 33 +/- 2 years) and ponderal index (22.9 +/- 1.3 versus 21.7 +/- 1.0). Glucose uptake was measured during steady state insulinaemia in the diabetic patients and control subjects, at euglycaemia (5.5 +/- 0.5 versus 5.4 +/- 0.3 mmol/l, respectively) and moderate hyperglycaemia (11.8 +/- 0.9 versus 10.2 +/- 0.7 mmol/l, respectively). At euglycaemia with similar free insulin levels (50 +/- 19 versus 43 +/- 9 mU/l; p greater than 0.6), the diabetic patients utilized less glucose than the control subjects (27.8 +/- 4.2 versus 56.4 +/- 5.7 mumol.kg-1.min-1;.p less than 0.005). During hyperglycaemia, the diabetic patients utilized almost as much glucose as the control subjects did at euglycaemia (49.9 +/- 6.4 versus 56.4 +/- 5.7 mumol.kg-1.min-1, respectively). In the control subjects, a 1-mmol/l rise in glucose concentration (with insulin remaining constant) resulted in a 12.3 +/- 1.3 mumol.kg-1.min-1 rise in glucose utilization. In contrast, in the diabetic patients, a 1-mmol/l rise in blood glucose resulted in a rise in glucose utilization of only 3.8 +/- 0.8 mumol.kg-1.min-1 (p less than 0.001), in the presence of similar concentrations of plasma insulin. This defect of glucose utilization in Type1 diabetic patients could not be reversed by acutely raising insulin to 247 +/- 23 mU/l.(ABSTRACT TRUNCATED AT 250 WORDS)

Insulin resistance in Type 1 (insulin-dependent) diabetes: dependence on plasma insulin concentration

“…In a recent report, Proietto et al showed that glucose utilisation was markedly reduced in poorly-controlled Type1 diabetic subjects with long-standing diabetes but, in contrast to our findings, this defect could not be corrected by hyperinsulinaemia [9]. Two points can be raised in view of this apparent discrepancy between our two studies.…”

“…It has been shown that hepatic glucose production can be inhibited easily by insulin both in Type 1 diabetes [8,9,19,20] and in non-diabetic subjects [8,10,20] and that plasma insulin levels of approximately 50 mU/1 cause a 70% or more suppression of hepatic glucose production [8][9][10]. Thus, in our study, hepatic glucose production should have been suppressed to a major extent at the second, third and fourth insulin infusion rates both in diabetic and non-diabetic subjects, and glucose infusion rates during these periods could be equated with glucose disposal rates.…”

“…In one, where diabetes was of recent onset, nine out of 12 subjects had insulin sensitivity similar to that of controis [6]. In the other three studies [7][8][9], where the subjects had long-standing diabetes, insulin-mediated glucose utilization was markedly reduced in diabetic subjects, both under hyperglycaemic and euglycaemic conditions [8,9].The present study was undertaken to define more precisely the responsiveness to insulin in vivo in longstanding Type 1 diabetes. Studies in vitro have shown in many pathological conditions that abnormal tissue response to insulin is not seen over the full insulin dose response curve, but may be restricted to a relatively narrow range of insulin concentrations.…”

“…In one, where diabetes was of recent onset, nine out of 12 subjects had insulin sensitivity similar to that of controis [6]. In the other three studies [7][8][9], where the subjects had long-standing diabetes, insulin-mediated glucose utilization was markedly reduced in diabetic subjects, both under hyperglycaemic and euglycaemic conditions [8,9].…”

Low-Protein, Low-Phosphorus Diet and Tissue Insulin Sensitivity in Insulin-Dependent Diabetic Patients with Chronic Renal Failure

“…De Fronzo et al [10] demonstrated that the sup pression o f hepatic glucose production by insulin in uremic patients was similar to that observed in a control group with normal renal function. A similar suppression o f hepatic glucose production was shown in insulintreated patients with normal renal function [11]. There fore, the improvement in response to exogenous insulin observed in the clamp study during LPD can be attri buted to the reduced insulin resistance of extrasplanchnic tissues.…”